Thereispathologicaldamagetothepancreaticbetacells.Insulinitiswithpancreaticmononuclearcellinfiltrationisacharacteristicfeatureattheonsetofthedisorder.Cytokinesmaybeinvolvedintheearlydestructionofthepancreas.
3.
PeoplewithT1DMarepronetoketoacidosis.
4.
Ninetypercentofcasesbegininchildhood,mostlybetween10and14yearsofage.Thiscommonobservationledtoapplicationofthetermjuvenile diabetes tothedisorder.ThistermisnolongerusedbecauseT1DMcanariseatanytimeoflife,althoughjuvenileonsetisthetypicalpattern.
5.
Isletcellautoantibodiesarefrequentlypresentaroundthetimeofonset.IfT1DMisinducedbyavirus,theautoantibodiesaretransient.Occasionallyantibodieswillpersistlongterm,particularlyiftheyareassociatedwithotherautoimmunedisorders.About50%ofT1DMisrelatedtoproblemswiththemajorhistocompatibilitycomplexonchromosome6.Itiscorrelatedwithanincreasedfrequencyofcertainhumanleukocyteantigen(HLA)alleles.TheHLAtypesDR3andDR4aremostcommonlyassociatedwithdiabetes.
who received poor nutrition and into a life that meant chronic undernourishment.
A measure of adiposity is the body mass index (BMI). The BMI of an individual is calculated as:
Equation 38.1
The BMI of healthy lean individuals ranges from 20 to 25. A BMI greater than 25 indicates that the individual is overweight, whereas a BMI higher than 30 indicates obesity. The condition of being overweight or obese is a risk factor for multiple pathologies, including insulin resistance, dyslipidemia, diabetes, cardiovascular disease, and hypertension.
WAT tissue is divided into subcutaneous and intraabdominal (visceral) depots. Intraabdominal WAT refers primarily to omental and mesenteric fat and is the smaller of the two depots. These depots receive different blood supplies that are drained in a fundamentally different way in that venous return from intraabdominal fat leads into the hepatic portal system. Thus intraabdominally derived FFAs are mostly cleared by the liver, whereas subcutaneous fat is the primary site for providing FFAs to muscle during exercise or fasting. Regulation of intraabdominal and subcutaneous adipose tissue also differs. Abdominal fat is highly innervated by autonomic neurons and has a greater turnover rate. Furthermore, these two depots display differences in hormone production and enzyme activity.
Men tend to gain fat in the intraabdominal depot (android [apple-shaped] adiposity), whereas women tend to gain fat in the subcutaneous depot, particularly in the thighs and buttocks (gynecoid [pear-shaped] adiposity). Clearly an excess of abdominal fat poses a greater risk factor for the pathologies mentioned earlier. Thus another indicator of body composition is circumference of the waist (measured in inches around the narrowest point between the ribs and hips when viewed from the front after exhaling) divided by the circumference of the hips (measured at the point where the buttocks are largest when viewed from the side). This waist-hip ratio may be a better indicator of body fat than BMI, especially as it relates to risk for development of diseases. A waist-hip ratio of greater than 0.95 in men or 0.85 in women is linked to a significantly higher risk for development of diabetes and cardiovascular disease.
In recent years, numerous hormones and neuropeptides have been implicated in both chronic and acute regulation of appetite, satiety, and energy expenditure in humans. One
CHAPTER 39 Hormonal Regulation of Energy Metabolism simplified model involves two peptide hormones, leptin